#Taiwan #Taipei #AnnJi Pharmaceutical #AJ201 #SBMA

AnnJi Pharmaceutical's Promising Phase 1/2a Findings for SBMA

AnnJi Pharmaceutical Co., Ltd., a clinical-stage biotechnology firm from Taiwan, has unveiled positive results from its Phase 1/2a trial of AJ201, a novel treatment aimed at Spinal and Bulbar Muscular Atrophy (SBMA). The trial was structured as a randomized, double-blind, placebo-controlled study involving adults diagnosed with this rare neuromuscular disorder. Conducted across six clinical sites in the United States, this trial assessed not only the drug's safety and tolerability but also its pharmacokinetic and pharmacodynamic properties (ClinicalTrials.gov Identifier NCT05517603). Although the study was not designed primarily to establish efficacy, the exploratory endpoints indicated significant therapeutic benefits that warrant further investigation.

Safety and Pharmacokinetics Assessment

The safety profile of AJ201 in SBMA patients mirrored results from previous trials in healthy volunteers, underscoring the drug's favorable tolerability. Notably, no systemic accumulation of the drug was noted during the study, suggesting a reassuring safety margin for patients at this early stage of treatment.

Clinical Efficacy Signals

After receiving AJ201 orally for three months, patients demonstrated significant enhancements in both physical and muscular function compared to those on placebo. Key improvements included an average increase of 17.6 meters in the 6-Minute Walk Test (6MWT) and a mean rise of 0.8 points on the SBMA Functional Rating Scale (SBMAFRS). In contrast, participants in the placebo group experienced minor declines, reinforcing the potential benefits of AJ201. Improvements were also observed in serum biomarkers, with AJ201 recipients showing reductions in both creatine kinase and myoglobin levels, heralding positive therapeutic implications. Specifically, 11 out of 15 participants in the AJ201 group showed positive responses in the 6MWT, along with impressive results in the other assessed areas, signaling a robust efficacy profile.

Biomarker and Mechanistic Insights

The trial utilized muscle biopsies to assess mutant androgen receptor (mAR) levels, a biomarker associated with SBMA. Remarkably, over half of the AJ201-treated participants exhibited a more than 50% reduction in nuclear mAR levels, markedly superior to the 17% observed in the placebo group, thus hinting at AJ201's therapeutic activity. Further RNA sequencing analysis of muscle samples from patients receiving AJ201 illuminated the activation of the Nrf2 signaling pathway, along with modulation of various other critical signaling cascades—findings absent in the placebo cohort, thus bolstering support for AJ201's proposed mechanism of action.

Conclusion and Professional Insights

"The outcomes of this study are incredibly promising. AJ201 has demonstrated meaningful clinical benefits, indicated by enhancements in functional assessments and encouraging serum biomarker shifts, coupled with RNA sequencing data affirming the activation of disease-modulating pathways," commented Dr. Christopher Grunseich, Principal Investigator of the study and a noteworthy figure within the NIH. He encapsulated the significance of the findings within the context of SBMA, a slowly progressing neuromuscular disorder, expressing optimism over the short-term treatment effects observed in participants.

Wendy Huang, Ph.D., CEO of AnnJi, also shared her enthusiasm: "We remain dedicated to advancing AJ201 to Phase 3 trials, aiming to offer a safe and effective treatment for SBMA—a condition that currently lacks FDA-approved options."

Understanding SBMA and AJ201

SBMA, commonly referred to as Kennedy's disease, is a rare X-linked inherited neuromuscular disorder stemming from CAG repeat expansions in the androgen receptor gene. This mutation propagates muscle and neuronal degeneration through toxic processes, oxidative stress, and neuroinflammation. With a global incidence of approximately 1 in 40,000 males, the urgency for effective treatments is pressing. AJ201, also known as JM17, has presented promising preclinical efficacy in reducing mutant AR toxicity and enhancing motor function. Mechanistically, it facilitates the breakdown of harmful mAR proteins and prompts the expression of protective enzymes, positing itself as a hopeful candidate in the quest to mitigate SBMA progression.

About AnnJi Pharmaceutical

Founded in 2014, AnnJi Pharmaceutical Co., Ltd. is dedicated to the development of breakthrough small-molecule therapies addressing significant gaps in medical care across various domains, including neurology and rare diseases such as SBMA. The company is prioritizing scientific advancement and collaboration to transform research into innovative and efficacious treatments. For more details, please visit www.ajpharm.com.

Disclaimer: This release contains forward-looking statements based on current assumptions and subject to risks and uncertainties that may influence actual outcomes.